Search results for "hemic and immune systems"
showing 10 items of 340 documents
Human CD4+CD25+ T cells derived from the majority of atopic donors are able to suppress TH1 and TH2 cytokine production
2003
Abstract Background: Recently, it has been established that CD4 + CD25 + T cells with regulatory capacity are present in human peripheral blood, inhibiting allogeneic proliferation and cytokine production of preactivated CD4 + CD25 − respond-er T cells. Objective: The aim of this study was to analyze in an allergen-specific setting whether such regulatory CD4 + CD25 + T cells also exist and function normally in atopic individuals, especially concerning the inhibition of T H 2 cytokines. Methods: For this purpose, CD4 + CD25 − or CD4 + CD25 + T cells from donors allergic to grass or birch pollen (mainly with rhinitis) or from healthy nonatopic donors were stimulated in the presence of autolo…
AML-associated Flt3 kinase domain mutations show signal transduction differences compared with Flt3 ITD mutations
2005
Activating mutations of Flt3 are found in approximately one third of patients with acute myeloid leukemia (AML) and are an attractive drug target. Two classes of Flt3 mutations occur: internal tandem duplications (ITDs) in the juxtamembrane and point mutations in the tyrosine kinase domain (TKD). We and others have shown that Flt3-ITD induced aberrant signaling including strong activation of signal transducer and activator of transcription 5 (STAT5) and repression of CCAAT/estradiol-binding protein α (c/EBPα) and Pu.1. Here, we compared the signaling properties of Flt3-ITD versus Flt3-TKD in myeloid progenitor cells. We demonstrate that Flt3-TKD mutations induced autonomous growth of 32D ce…
CD4-mediated functional activation of human CD4+CD25+ regulatory T cells
2007
Naturally occurring CD4(+)CD25(+)FoxP3(+) regulatory T cells (CD25(+) Tregs) constitute a specialized population of T cells that is essential for the maintenance of peripheral self-tolerance. The immune regulatory function of CD25(+) Tregs depends upon their activation. We found that anti-CD4 antibodies activate the suppressive function of human CD25(+) Tregs in a dose-dependent manner. We demonstrate that CD4-activated CD25(+) Tregs suppress the proliferation of CD4(+) and CD8(+) T cells, their IL-2 and IFN-gamma production as well as the capacity of CD8(+) T cells to re-express CD25. By contrast, anti-CD4 stimulation did not induce suppressive activity in conventional CD4(+) T cells. Thes…
Protection from graft-versus-host disease by HIV-1 envelope protein gp120-mediated activation of human CD4+CD25+ regulatory T cells.
2009
AbstractNaturally occurring CD4+CD25+ regulatory T cells (Tregs) represent a unique T-cell lineage that is endowed with the ability to actively suppress immune responses. Therefore, approaches to modulate Treg function in vivo could provide ways to enhance or reduce immune responses and lead to novel therapies. Here we show that the CD4 binding human immunodeficiency virus-1 envelope glycoprotein gp120 is a useful and potent tool for functional activation of human Tregs in vitro and in vivo. Gp120 activates human Tregs by binding and signaling through CD4. Upon stimulation with gp120, human Tregs accumulate cyclic adenosine monophosphate (cAMP) in their cytosol. Inhibition of endogeneous cA…
Differentiation of Effector/Memory Vδ2 T Cells and Migratory Routes in Lymph Nodes or Inflammatory Sites
2003
Vδ2 T lymphocytes recognize nonpeptidic antigens without presentation by MHC molecules and mount both immediate effector functions and memory responses after microbial infection. However, how Vδ2 T cells mediate different facets of a memory response remains unknown. Here, we show that the expression of CD45RA and CD27 antigens defines four subsets of human Vδ2 T cells with distinctive compartmentalization routes. Naive CD45RA+CD27+ and memory CD45RA−CD27+ cells express lymph node homing receptors, abound in lymph nodes, and lack immediate effector functions. Conversely, memory CD45RA−CD27− and terminally differentiated CD45RA+CD27− cells, which express receptors for homing to inflamed tissu…
Prevention and reversal of superantigen-induced anergy by contact allergen exposure
1995
The superantigen Staphylococcal enterotoxin B (SEB) and the contact allergen 2,4-dinitrofluorbenzene (DNFB) both react with V beta 8+ T-cells delivering distinct signals. Pre-treatment with DNFB painted onto the same skin site where SEB was to be injected, prevented the induction of anergy in V beta + T-cells that was otherwise induced after SEB had been injected intradermally over a period of 2 weeks. Application of the irritant sodium dodecyl sulfate (SDS) instead of DNFB did not exert this effect. Application of DNFB at a site distant from the site where SEB was injected resulted in a much weaker inhibitory influence on the induction of anergy by SEB. Established anergy of V beta 8+ T-ce…
Interleukin-12 and -23 Control Plasticity of CD127(+) Group 1 and Group 3 Innate Lymphoid Cells in the Intestinal Lamina Propria.
2015
Human group 1 ILCs consist of at least three phenotypically distinct subsets, including NK cells, CD127(+) ILC1, and intraepithelial CD103(+) ILC1. In inflamed intestinal tissues from Crohn's disease patients, numbers of CD127(+) ILC1 increased at the cost of ILC3. Here we found that differentiation of ILC3 to CD127(+) ILC1 is reversible in vitro and in vivo. CD127(+) ILC1 differentiated to ILC3 in the presence of interleukin-2 (IL-2), IL-23, and IL-1β dependent on the transcription factor RORγt, and this process was enhanced in the presence of retinoic acid. Furthermore, we observed in resection specimen from Crohn's disease patients a higher proportion of CD14(+) dendritic cells (DC), whi…
IL-2, IL-3, and IFN-gamma differently affect in vivo frequencies of circulating precursors of cytotoxic T lymphocytes (CTL-p)
1993
Experimental animal and human in vivo studies have previously demonstrated the impact of exogenous administration of various cytokines on frequencies of circulating myeloid and LAK precursor cells. For the first time we investigated whether exogenous cytokines, in the absence of antigenic challenge, may also influence frequencies of circulating antigen-specific cytotoxic T-lymphocyte precursor cells. We further asked whether triggering of autoimmune pathways as has been reported for several cytokines can be confirmed on the cellular level by demonstration of induction of autoreactive CTL-p. Limiting dilution analysis was used to determine alloreactive CTL-p frequencies in 31 patients with n…
Targeting IL-6 signalling in early rheumatoid arthritis is followed by Th1 and Th17 suppression and Th2 expansion.
2014
OBJECTIVES: To investigate the in vitro and ex-vivo effect of IL-6 inhibition on the balance between Th1, Th2, Th17 and Treg cells. METHODS: Ten consecutive adult patients with active early rheumatoid arthritis (ERA) and ten healthy volunteers were included in the study. The percentages of Th1, Th2, Th17 and Treg cells were analysed by flow cytometry in the peripheral blood mononuclear cells obtained from controls and from RA patients at the time of first evaluation and just before the third TCZ infusion. The in vitro effect of TCZ on the different subsets of CD4+ T cells and the expression levels of Th1, Th2, Th17 and Treg-related cytokines was also assessed. RESULTS: Treatment with TCZ, b…
Functionally Active T Cell Receptor/CD3 Complexes Are Present at the Surface of Cloned Cytotoxic T Cells without Fluorescence-Immunological Detectabi…
1996
The cytotoxic T cell clone 10BK.1 is activated in response to the ovalbumin peptide OVA257-264 in a major histocompatibility complex class I-restricted manner. Following activation 10BK.1 cells proliferate, secrete lymphokines, and kill syn- and allogeneic target cells. Using immunofluorescence analysis we detected CD8, LFA-1, and ICAM-1 on the surface of 10BK.1 cells, but no CD3 or T cell receptor (TCR). In contrast, the proliferative response of 10BK.1 cells to antigen was efficiently blocked by soluble antibodies directed at CD3 epsilon or TCR alpha beta, but not by antibodies directed at TCR gamma delta. In addition, lysis of target cells was blocked by F(ab')2 fragments of antibodies d…